Details

Autor(en) / Beteiligte

• Leonardi, Emanuela
• Bettella, Elisa
• Pelizza, Maria Federica
• Aspromonte, Maria Cristina
• Polli, Roberta
• Boniver, Clementina
• Sartori, Stefano
• Milani, Donatella
• Murgia, Alessandra

Titel

Identification of SETBP1 Mutations by Gene Panel Sequencing in Individuals With Intellectual Disability or With "Developmental and Epileptic Encephalopathy"

Ist Teil von

• Frontiers in neurology, 2020-12, Vol.11, p.593446-593446

Ort / Verlag

Switzerland: Frontiers Research Foundation

Erscheinungsjahr

2020

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• mutations are associated with the Schinzel-Giedion syndrome (SGS), characterized by profound neurodevelopmental delay, typical facial features, and multiple congenital malformations (OMIM 269150). Refractory epilepsy is a common feature of SGS. Loss of function mutations have been typically associated with a distinct and milder phenotype characterized by intellectual disability and expressive speech impairment. Here we report three variants of , two novel truncating mutations, identified by NGS analysis of an Intellectual Disability gene panel in 600 subjects with non-specific neurodevelopmental disorders, and one missense identified by a developmental epilepsy gene panel tested in 56 pediatric epileptic cases. The three individuals carrying the identified variants presented mild to severe developmental delay and lacked the cardinal features of classical SGS. One of these subjects, carrying the c.1765C>T (p.Arg589 ) mutation, had mild Intellectual Disability with speech delay; the second one carrying the c.2199_2203del (p.Glu734Alafs19 ) mutation had generalized epilepsy, responsive to treatment, and moderate Intellectual Disability; the third patient showed a severe cognitive defects and had a history of drug resistant epilepsy with West syndrome evolved into a Lennox-Gastaut syndrome. This latter subject carries the missense c.2572G>A (p.Glu858Lys) variant, which is absent from the control population, reported as in a subject with ASD, and located close to the hot spot for SGS-associated mutations. Our findings contribute to further characterizing the associated phenotypes and suggest inclusion of in the list of prioritized genes for the genetic diagnosis of overlapping phenotypes ranging from non-specific neurodevelopmental disorders to "developmental and epileptic encephalopathy" (DEE).